Periodic breathing in heart failure patients: testing the hypothesis of instability of the chemoreflex loop.

In this study, we applied time- and frequency-domain signal processing techniques to the analysis of respiratory and arterial O(2) saturation (Sa(O(2))) oscillations during nonapneic periodic breathing (PB) in 37 supine awake chronic heart failure patients. O(2) was administered to eight of them at 3 l/min. Instantaneous tidal volume and instantaneous minute ventilation (IMV) signals were obtained from the lung volume signal. The main objectives were to verify 1) whether the timing relationship between IMV and Sa(O(2)) was consistent with modeling predictions derived from the instability hypothesis of PB and 2) whether O(2) administration, by decreasing loop gain and increasing O(2) stores, would have increased system stability reducing or abolishing the ventilatory oscillation. PB was centered around 0.021 Hz, whereas respiratory rate was centered around 0.33 Hz and was almost stable between hyperventilation and hypopnea. The average phase shift between IMV and Sa(O(2)) at the PB frequency was 205 degrees (95% confidence interval 198-212 degrees). In 12 of 37 patients in whom we measured the pure circulatory delay, the predicted lung-to-ear delay was 28.8 +/- 5.2 s and the corresponding observed delay was 30.9 +/- 8.8 s (P = 0.13). In seven of eight patients, O(2) administration abolished PB (in the eighth patient, Sa(O(2)) did not increase). These results show a remarkable consistency between theoretical expectations derived from the instability hypothesis and experimental observations and clearly indicate that a condition of loss of stability in the chemical feedback control of ventilation might play a determinant role in the genesis of PB in awake chronic heart failure patients.     

New insight into the mechanism of cardiovascular dysfunction in the elderly: transfer function analysis

This study sought to test the hypothesis that alterations in the relationships between (i) mean arterial pressure (MAP) and heart rate (HR), (ii) cardiac output (CO) and MAP, and (iii) total peripheral resistance (TPR) and MAP variability contribute to the diminished dynamic control of cardiovascular function with advanced age. Six-minute hemodynamic data were continuously recorded in 11 elderly (70 +/- 2 years) and 11 young (26 +/- 1 year) healthy volunteers under supine resting condition and during lower body negative pressure-induced orthostatic challenge. The data were converted using fast Fourier transform, and the ratio of cross-spectra to auto-spectra between two signals (i.e., MAP-HR, CO-MAP, TPR-MAP) was computed for transfer function analysis. In the low-frequency ranges (LF; 0.04-0.14 Hz) and high-frequency ranges (0.15-0.30 Hz), the gain and coherence of the transfer function describing the relationship between MAP-HR signals were significantly greater in younger than in older adults. The phase degree was significantly >0 in both groups under all conditions, suggesting that the MAP variability preceded the HR variability. In contrast, the coherence between CO-MAP signals in both age groups was <0.5, indicating that the beat-to-beat MAP variability was not significantly related to the CO signals. However, the transfer function gain and coherence of TPR-MAP signals were significantly greater in the young group (coherence >/=0.5 in the LF range), suggesting a more effective dynamic vasomotor control. In conclusion, the oscillations in CO-MAP signals are not significantly synchronized or not related in a simply linear fashion in both age groups. The MAP variability is more related to the oscillation of TPR signals in the young group only. Advanced age not only diminishes MAP-HR transfer function gain, but also weakens its coherence. Thus, alterations in the relationship between MAP-HR variability and TPR-MAP variability may significantly contribute to the diminished dynamic control of cardiovascular function manifest in the elderly.     

Detection of low- and high-frequency rhythms in the variability of skin sympathetic nerve activity

Spectral analysis of skin blood flow has demonstrated low-frequency (LF, 0.03-0.15 Hz) and high-frequency (HF, 0.15-0.40 Hz) oscillations, similar to oscillations in R-R interval, systolic pressure, and muscle sympathetic nerve activity (MSNA). It is not known whether the oscillatory profile of skin blood flow is secondary to oscillations in arterial pressure or to oscillations in skin sympathetic nerve activity (SSNA). MSNA and SSNA differ markedly with regard to control mechanisms and morphology. MSNA contains vasoconstrictor fibers directed to muscle vasculature, closely regulated by baroreceptors. SSNA contains both vasomotor and sudomotor fibers, differentially responding to arousals and thermal stimuli. Nevertheless, MSNA and SSNA share certain common characteristics. We tested the hypothesis that LF and HF oscillatory components are evident in SSNA, similar to the oscillatory components present in MSNA. We studied 18 healthy normal subjects and obtained sequential measurements of MSNA and SSNA from the peroneal nerve during supine rest. Measurements were also obtained of the electrocardiogram, beat-by-beat blood pressure (Finapres), and respiration. Spectral analysis showed LF and HF oscillations in MSNA, coherent with similar oscillations in both R-R interval and systolic pressure. The HF oscillation of MSNA was coherent with respiration. Similarly, LF and HF spectral components were evident in SSNA variability, coherent with corresponding variability components of R-R interval and systolic pressure. HF oscillations of SSNA were coherent with respiration. Thus our data suggest that these oscillations may be fundamental characteristics shared by MSNA and SSNA, possibly reflecting common central mechanisms regulating sympathetic outflows subserving different regions and functions.     

Feedback effects of circulating norepinephrine on sympathetic outflow in healthy subjects

The amplitude of low-frequency (LF) oscillations of heart rate (HR) usually reflects the magnitude of sympathetic activity, but during some conditions, e.g., physical exercise, high sympathetic activity results in a paradoxical decrease of LF oscillations of HR. We tested the hypothesis that this phenomenon may result from a feedback inhibition of sympathetic outflow caused by circulating norepinephrine (NE). A physiological dose of NE (100 ng.kg(-1).min(-1)) was infused into eight healthy subjects, and infusion was continued after alpha-adrenergic blockade [with phentolamine (Phe)]. Muscle sympathetic nervous activity (MSNA) from the peroneal nerve, LF (0.04-0.15 Hz) and high frequency (HF; 0.15-0.40 Hz) spectral components of HR variability, and systolic blood pressure variability were analyzed at baseline, during NE infusion, and during NE infusion after Phe administration. The NE infusion increased the mean blood pressure and decreased the average HR (P < 0.01 for both). MSNA (10 +/- 2 vs. 2 +/- 1 bursts/min, P < 0.01), LF oscillations of HR (43 +/- 13 vs. 35 +/- 13 normalized units, P < 0.05), and systolic blood pressure (3.1 +/- 2.3 vs. 2.0 +/- 1.1 mmHg2, P < 0.05) decreased significantly during the NE infusion. During the NE infusion after PHE, average HR and mean blood pressure returned to baseline levels. However, MSNA (4 +/- 2 bursts/min), LF power of HR (33 +/- 9 normalized units), and systolic blood pressure variability (1.7 +/- 1.1 mmHg2) remained significantly (P < 0.05 for all) below baseline values. Baroreflex gain did not change significantly during the interventions. Elevated levels of circulating NE cause a feedback inhibition on sympathetic outflow in healthy subjects. These inhibitory effects do not seem to be mediated by pressor effects on the baroreflex loop but perhaps by a presynaptic autoregulatory feedback mechanism or some other mechanism that is not prevented by a nonselective alpha-adrenergic blockade.     

Long-term measurement of heart rate in chicken eggs

Taking advantage of acoustocardiogram (ACG), we measured the heart rate (HR) of chick embryos continuously from day 12 until hatching and then investigated the development of HR irregularities (HRI), HR variability (HRV), and the existence of a circadian rhythm in mean HR (MHR). HRI comprised transient bradycardia and tachycardia, which first developed on day 14 and 16 in most embryos, respectively. Transient bradycardia increased in frequency and magnitude with embryonic development and occurred over periods of up to 30 min in some embryos. MHR was maximal on around days 14-15 and thereafter decreased to about 250-260 bpm on days 16-18. Baseline HRV, which is an oscillation of the MHR baseline, occurred as HR decreased from days 15-16 and became predominant on days 17-18. The magnitude of the baseline oscillations reached up to 50 bpm in some embryos and the period ranged between about 40-90 min (ultradian rhythm). A circadian rhythm of MHR was not found in late chick embryos. On days 18-19, embryonic activities were augmented and then breathing movements began to occur, disturbing ACG signals and thus making it difficult to measure the HR. Instead, the development of breathing activities was recorded. Breathing frequency was irregular at first and then increased to a maximum of about 1.5 Hz prior to hatching.     

Alterations in cerebral autoregulation and cerebral blood flow velocity during acute hypoxia: rest and exercise

We examined the relationship between changes in cardiorespiratory and cerebrovascular function in 14 healthy volunteers with and without hypoxia [arterial O(2) saturation (Sa(O(2))) approximately 80%] at rest and during 60-70% maximal oxygen uptake steady-state cycling exercise. During all procedures, ventilation, end-tidal gases, heart rate (HR), arterial blood pressure (BP; Finometer) cardiac output (Modelflow), muscle and cerebral oxygenation (near-infrared spectroscopy), and middle cerebral artery blood flow velocity (MCAV; transcranial Doppler ultrasound) were measured continuously. The effect of hypoxia on dynamic cerebral autoregulation was assessed with transfer function gain and phase shift in mean BP and MCAV. At rest, hypoxia resulted in increases in ventilation, progressive hypocapnia, and general sympathoexcitation (i.e., elevated HR and cardiac output); these responses were more marked during hypoxic exercise (P < 0.05 vs. rest) and were also reflected in elevation of the slopes of the linear regressions of ventilation, HR, and cardiac output with Sa(O(2)) (P < 0.05 vs. rest). MCAV was maintained during hypoxic exercise, despite marked hypocapnia (44.1 +/- 2.9 to 36.3 +/- 4.2 Torr; P < 0.05). Conversely, hypoxia both at rest and during exercise decreased cerebral oxygenation compared with muscle. The low-frequency phase between MCAV and mean BP was lowered during hypoxic exercise, indicating impairment in cerebral autoregulation. These data indicate that increases in cerebral neurogenic activity and/or sympathoexcitation during hypoxic exercise can potentially outbalance the hypocapnia-induced lowering of MCAV. Despite maintaining MCAV, such hypoxic exercise can potentially compromise cerebral autoregulation and oxygenation.     

Cardiac rhythms in developing emu hatchlings

Six emu hatchlings were non-invasively measured for electrocardiogram (ECG) from their chest wall using flexible electrodes, and the instantaneous heart rate (IHR) was determined from ECG throughout the first week of post-hatching life. Although the baseline heart rate (HR) was low, approximately 100-200 beats per min (bpm), compared with chick hatchlings, the IHR fluctuated markedly. The fluctuation of IHR comprised HR variability and irregularities that were designated as types I, II and III in chick hatchlings and additional large accelerations distinctive of emu hatchlings. Type I was HR oscillation with a mean frequency of 0.37 Hz (range 0.2-0.7 Hz), i.e. respiratory sinus arrhythmia (RSA). From RSA, breathing frequency in emu hatchlings was estimated to be approximately half of that in chickens. Type II HR oscillation was also found in the emu; the frequency ranged from approximately 0.04 to 0.1 with a mean of 0.06 Hz, and the magnitude tended to be large compared with that of chickens. In addition to type III HRI, which was designated in chickens, large, irregular HR accelerations were characteristic of emu hatchlings. From IHR data, developmental patterns of mean heart rate (MHR) were constructed and plotted on a single graph to inspect the diurnal rhythm of MHR by visual inspection and power spectrum analysis. A circadian rhythm was not clear in the emu hatchlings, in contrast to chick hatchlings, which showed a dominant diurnal rhythm.     

Lung and chest wall mechanics in rabbits during high-frequency body-surface oscillation

In eight anesthetized and tracheotomized rabbits, we studied the transfer impedances of the respiratory system during normocapnic ventilation by high-frequency body-surface oscillation from 3 to 15 Hz. The total respiratory impedance was partitioned into pulmonary and chest wall impedances to characterize the oscillatory mechanical properties of each component. The pulmonary and chest wall resistances were not frequency dependent in the 3- to 15-Hz range. The mean pulmonary resistance was 13.8 +/- 3.2 (SD) cmH2O.l-1.s, although the mean chest wall resistance was 8.6 +/- 2.0 cmH2O.l-1.s. The pulmonary elastance and inertance were 0.247 +/- 0.095 cmH2O/ml and 0.103 +/- 0.033 cmH2O.l-1.s2, respectively. The chest wall elastance and inertance were 0.533 +/- 0.136 cmH2O/ml and 0.041 +/- 0.063 cmH2O.l-1.s2, respectively. With a linear mechanical behavior, the transpulmonary pressure oscillations required to ventilate these tracheotomized animals were at their minimal value at 3 Hz. As the ventilatory frequency was increased beyond 6-9 Hz, both the minute ventilation necessary to maintain normocapnia and the pulmonary impedance increased. These data suggest that ventilation by body-surface oscillation is better suited for relatively moderate frequencies in rabbits with normal lungs.     

Oxygen-conserving effects of apnea in exercising men.

We sought to determine whether apnea-induced cardiovascular responses resulted in a biologically significant temporary O(2) conservation during exercise. Nine healthy men performing steady-state leg exercise carried out repeated apnea (A) and rebreathing (R) maneuvers starting with residual volume +3.5 liters of air. Heart rate (HR), mean arterial pressure (MAP), and arterial O(2) saturation (Sa(O(2)); pulse oximetry) were recorded continuously. Responses (DeltaHR, DeltaMAP) were determined as differences between HR and MAP at baseline before the maneuver and the average of values recorded between 25 and 30 s into each maneuver. The rate of O(2) desaturation (DeltaSa(O(2))/Deltat) was determined during the same time interval. During apnea, DeltaSaO(2)/Deltat had a significant negative correlation to the amplitudes of DeltaHR and DeltaMAP (r(2) = 0.88, P < 0.001); i.e., individuals with the most prominent cardiovascular responses had the slowest DeltaSa(O(2))/Deltat. DeltaHR and DeltaMAP were much larger during A (-44 +/- 8 beats/min, +49 +/- 4 mmHg, respectively) than during R maneuver (+3 +/- 3 beats/min, +30 +/- 5 mmHg, respectively). DeltaSa(O(2))/Deltat during A and R maneuvers was -1.1 +/- 0.1 and -2.2 +/- 0.2% units/s, respectively, and nadir Sa(O(2)) values were 58 +/- 4 and 42 +/- 3% units, respectively. We conclude that bradycardia and hypertension during apnea are associated with a significant temporary O(2) conservation and that respiratory arrest, rather than the associated hypoxia, is essential for these responses.     

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

The effect of exercise-induced arterial hypoxemia (EIAH) on quadriceps muscle fatigue was assessed in 11 male endurance-trained subjects [peak O2 uptake (VO2 peak) = 56.4 +/- 2.8 ml x kg(-1) x min(-1); mean +/- SE]. Subjects exercised on a cycle ergometer at >or=90% VO2 peak) to exhaustion (13.2 +/- 0.8 min), during which time arterial O2 saturation (Sa(O2)) fell from 97.7 +/- 0.1% at rest to 91.9 +/- 0.9% (range 84-94%) at end exercise, primarily because of changes in blood pH (7.183 +/- 0.017) and body temperature (38.9 +/- 0.2 degrees C). On a separate occasion, subjects repeated the exercise, for the same duration and at the same power output as before, but breathed gas mixtures [inspired O2 fraction (Fi(O2)) = 0.25-0.31] that prevented EIAH (Sa(O2) = 97-99%). Quadriceps muscle fatigue was assessed via supramaximal paired magnetic stimuli of the femoral nerve (1-100 Hz). Immediately after exercise at Fi(O2) 0.21, the mean force response across 1-100 Hz decreased 33 +/- 5% compared with only 15 +/- 5% when EIAH was prevented (P < 0.05). In a subgroup of four less fit subjects, who showed minimal EIAH at Fi(O2) 0.21 (Sa(O2) = 95.3 +/- 0.7%), the decrease in evoked force was exacerbated by 35% (P < 0.05) in response to further desaturation induced via Fi(O2) 0.17 (Sa(O2) = 87.8 +/- 0.5%) for the same duration and intensity of exercise. We conclude that the arterial O2 desaturation that occurs in fit subjects during high-intensity exercise in normoxia (-6 +/- 1% DeltaSa(O2) from rest) contributes significantly toward quadriceps muscle fatigue via a peripheral mechanism.     

Ventilation by external high-frequency oscillation in cats

Eight anesthetized tracheostomized cats were placed in an 8.2-liter airtight chamber with the trachea connected to the exterior. Thirty-two combinations of high-frequency oscillations (HFO) (0.5-30 Hz; 25-100 ml) were delivered for 10 min each in random order into the chamber. Arterial blood gas tensions during oscillation were compared with control measurements made after 10 min of spontaneous breathing without oscillation when the mean arterial PCO2 (PaCO2) was 30.1 Torr. Ventilation due to spontaneous breathing (Vs) and oscillation (Vo) were derived from the chamber pressure trace and a pneumotachograph, respectively. As the oscillation frequency increased, oscillated tidal volume (Vo) decreased from a mean of 39 (0.5 Hz) to 3.3 ml (30 Hz) when 100 ml was delivered to the chamber. From 6-25 Hz, apnea occurred with Vo less than estimated respiratory dead space (VD); the minimum effective Vo/VD ratio was 0.37 +/- 0.05. Although Vo was maximal at 10 Hz at each oscillation volume, the lowest PaCO2 occurred at 2-6 Hz, and arterial PO2 rose as expected during hypocapnia. Above 10 Hz, PaCO2 was determined by Vo and was independent of frequency, whereas at lower frequencies, PaCO2 was related to Vo; below 6 Hz, PaCO2 varied inversely with the calculated alveolar ventilation. As oscillations became more effective, both PaCO2 and Vs fell progressively and were highly correlated; apnea occurred when PaCO2 was reduced by a mean of 4.5 Torr. Mean chamber pressure remained near zero up to 15 Hz, indicating functional residual capacity did not change. We conclude that externally applied HFO can readily maintain gas exchange in vivo, with Vo less than VD at frequencies over 2 Hz.     

Compliance of the main pulmonary artery during the ventilatory cycle.

Transmural pulmonary arterial pressure (Ppa), diameter (D), and length (L) of a segment of the main pulmonary artery (MPA) were measured simultaneously in anesthetized open-chest dogs. The instantaneous volume was calculated from D and L. Pulmonary arterial elasticity for diameter (EpD) was calculated as the ratio of the amplitude of Ppa to D oscillation normalized by the mean D. Similar indexes were calculated for L (EpL) and V (Epv). Compliance per unit length was calculated from the dimensions and elasticity of the MPA. Under control conditions with 5 cmH2O positive end-expiratory pressure, EpD, EpL, and Epv at cardiac frequency were 175 +/- 27, 147 +/- 27, and 55 +/- 7 cmH2O, respectively. EpD increased with positive end-expiratory pressure, but EpL decreased and Epv was unaffected. EpD, EpL, Epv, and compliance per unit length were not significantly different between the start of inspiration and the start of expiration. In addition, there were no significant phase differences between the oscillations of Ppa and V at respiratory frequency. We conclude that the previously reported time variation of pulmonary arterial compliance during the ventilatory cycle is not due to time-varying properties of the MPA.     

Pulmonary gas exchange in humans during normobaric hypoxic exercise

Previous studies (J. Appl. Physiol. 58: 978-988 and 989-995, 1985) have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during heavy exercise at sea level and during hypobaric hypoxia in a chamber [fractional inspired O2 concentration (FIO2) = 0.21, minimum barometric pressure (PB) = 429 Torr, inspired O2 partial pressure (PIO2) = 80 Torr]. We used the multiple inert gas elimination technique to compare gas exchange during exercise under normobaric hypoxia (FIO2 = 0.11, PB = 760 Torr, PIO2 = 80 Torr) with earlier hypobaric measurements. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate (HR), minute ventilation, respiratory rate (RR), and blood temperature were recorded at rest and during steady-state exercise in 10 normal subjects in the following order: rest, air; rest, 11% O2; light exercise (75 W), 11% O2; intermediate exercise (150 W), 11% O2; heavy exercise (greater than 200 W), 11% O2; heavy exercise, 100% O2 and then air; and rest 20 minutes postexercise, air. VA/Q inequality increased significantly during hypoxic exercise [mean log standard deviation of perfusion (logSDQ) = 0.42 +/- 0.03 (rest) and 0.67 +/- 0.09 (at 2.3 l/min O2 consumption), P less than 0.01]. VA/Q inequality was improved by relief of hypoxia (logSDQ = 0.51 +/- 0.04 and 0.48 +/- 0.02 for 100% O2 and air breathing, respectively). Diffusion limitation for O2 was evident at all exercise levels while breathing 11% O2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of the altitude level on cerebral autoregulation in residents at high altitude.

Cerebral autoregulation is impaired in Himalayan high-altitude residents who live above 4,200 m. This study was undertaken to determine the altitude at which this impairment of autoregulation occurs. A second aim of the study was to test the hypothesis that administration of oxygen can reverse this impairment in autoregulation at high altitudes. In four groups of 10 Himalayan high-altitude dwellers residing at 1,330, 2,650, 3,440, and 4,243 m, arterial oxygen saturation (Sa(O(2))), blood pressure, and middle cerebral artery blood velocity were monitored during infusion of phenylephrine to determine static cerebral autoregulation. On the basis of these measurements, the cerebral autoregulation index (AI) was calculated. Normally, AI is between zero and 1. AI of 0 implies absent autoregulation, and AI of 1 implies intact autoregulation. At 1,330 m (Sa(O(2)) = 97%), 2,650 m (Sa(O(2)) = 96%), and 3,440 m (Sa(O(2)) = 93%), AI values (mean +/- SD) were, respectively, 0.63 +/- 0.27, 0.57 +/- 0.22, and 0.57 +/- 0.15. At 4,243 m (Sa(O(2)) = 88%), AI was 0.22 +/- 0.18 (P < 0.0005, compared with AI at the lower altitudes) and increased to 0.49 +/- 0.23 (P = 0.008, paired t-test) when oxygen was administered (Sa(O(2)) = 98%). In conclusion, high-altitude residents living at 4,243 m have almost total loss of cerebral autoregulation, which improved during oxygen administration. Those people living at 3,440 m and lower have still functioning cerebral autoregulation. This study showed that the altitude region between 3,440 and 4,243 m, marked by Sa(O(2)) in the high-altitude dwellers of 93% and 88%, is a transitional zone, above which cerebral autoregulation becomes critically impaired.     

Unstable equilibrium behaviour in collapsible tubes

Thick-walled silicone rubber tube connected to rigid pipes upstream and downstream was externally pressurised (pe) to cause collapse while aqueous fluid flowed through propelled by a constant upstream head. Three types of equilibrium were found: stable equilibria (steady flow) at high downstream flow resistance R2, self-excited oscillations at low R2, and 'unattainable' (by varying external pressure) or exponentially unstable equilibria at intermediate R2. The self-excited oscillations were highly non-linear and appeared in four, apparently discrete, frequency bands: 2.7 Hz, 3.8-5.0 Hz, 12-16 Hz and 60-63 Hz, suggesting that the possible oscillation modes may be harmonically related. Stable, intermediate 'two-in-every-three-beats' oscillation was also observed, with a repetition frequency in the 3.8-5.0 Hz band. As pe was increased, self-excited oscillations were eventually suppressed, leaving internal fluid pressure varying with no single dominant frequency as a result of turbulent jet dissipation at the downstream rigid pipe connection. Comparison of pressure-wave velocity calculated from the local pressure-area relation for the tube with fluid velocity indicated that supercritical velocities were attained in the course of the self-excited oscillations.     

Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen

High altitude increases pulmonary arterial pressure (PAP), but no measurements have been made in humans above 4,500 m. Eight male athletic volunteers were decompressed in a hypobaric chamber for 40 days to a barometric pressure (PB) of 240 Torr, equivalent to the summit of Mt. Everest. Serial hemodynamic measurements were made at PB 760 (sea level), 347 (6,100 m), and 282/240 Torr (7,620/8,840 m). Resting PAP and pulmonary vascular resistance (PVR) increased from sea level to maximal values at PB 282 Torr from 15 +/- 0.9 to 34 +/- 3.0 mmHg and from 1.2 +/- 0.1 to 4.3 +/- 0.3 mmHg.l-1 X min, respectively. During near maximal exercise PAP increased from 33 +/- 1 mmHg at sea level to 54 +/- 2 mmHg at PB 282 Torr. Right atrial and wedge pressures were not increased with altitude. Acute 100% O2 breathing lowered cardiac output and PAP but not PVR. Systemic arterial pressure and resistance did not rise with altitude but did increase with O2 breathing, indicating systemic control differed from the lung circulation. We concluded that severe chronic hypoxia caused elevated pulmonary resistance not accompanied by right heart failure nor immediately reversed by O2 breathing.     

Altered frequency characteristic of central vasomotor control in SHR

Previous work from our laboratory has demonstrated that the very low-frequency (VLF: 0-0.25 Hz) and low-frequency (LF: 0.25-0.8 Hz) power of arterial pressure variability (APV) are related to vasomotor reactivity in response to control signals from the rostral ventrolateral medulla (RVLM) via the sympathetic system in the rat. The present study evaluated the differences in the dynamic property of central vasomotor control between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Experiments were carried out in 10- to 12-wk-old rats that were anesthetized with continuous infusion of pentobarbital sodium, paralyzed with pancuronium, and maintained on mechanical ventilation. We found that SHR exhibited significantly higher arterial pressure (AP), heart rate (HR), and VLF, LF, and high-frequency (0.8-2.4 Hz) power of APV than WKY under resting state. Broad-band electrical stimulation of the RVLM elicited parallel APV in the VLF and LF ranges in both rat strains. The evoked APV and transfer magnitude of the APV to stimulus spike rate variability (RVLM-AP magnitude) were significantly higher in SHR, especially in the LF range. The response frequency of central vasomotor control, represented by the high-cut frequency of RVLM-AP magnitude, was also extended in SHR. The disparity in RVLM-AP transfer magnitude between SHR and WKY became virtually absent after combined alpha- and beta-adrenoceptor blockade by phentolamine and propranolol. These results suggest that the dynamic control of RVLM on AP reactivity is enhanced in SHR, in which the adrenergic system may play a major role.     

Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia.

Patients with obstructive sleep apnea (OSA) have been reported to have an augmented pressor response to hypoxic rebreathing. To assess the contribution of the peripheral vasculature to this hemodynamic response, we measured heart rate, mean arterial pressure (MAP), and forearm blood flow by venous occlusion plethysmography in 13 patients with OSA and in 6 nonapneic control subjects at arterial oxygen saturations (Sa(O(2))) of 90, 85, and 80% during progressive isocapnic hypoxia. Measurements were also performed during recovery from 5 min of forearm ischemia induced with cuff occlusion. MAP increased similarly in both groups during hypoxia (mean increase at 80% Sa(O(2)): OSA patients, 9 +/- 11 mmHg; controls, 12 +/- 7 mmHg). Forearm vascular resistance, calculated from forearm blood flow and MAP, decreased in controls (mean change -37 +/- 19% at Sa(O(2)) 80%) but not in patients (mean change -4 +/- 16% at 80% Sa(O(2))). Both groups decreased forearm vascular resistance similarly after forearm ischemia (maximum change from baseline -85%). We conclude that OSA patients have an abnormal peripheral vascular response to isocapnic hypoxia.     

Role of membrane potential in vasomotion of isolated pressurized rat arteries

Vasomotion, the phenomenon of vessel diameter oscillation, regulates blood flow and resistance. The main parameters implicated in vasomotion are particularly the membrane potential and the cytosolic free calcium in smooth muscle cells. In this study, these parameters were measured in rat perfused-pressurized mesenteric artery segments. The application of norepinephrine (NE) caused rhythmic diameter contractions and membrane potential oscillations (amplitude; 5.3 +/- 0.3 mV, frequency; 0.09 +/- 0.01 Hz). Verapamil (1 microM) abolished this vasomotion. During vasomotion, 10(-5) M ouabain (Na(+)-K(+) ATPase inhibitor) decreased the amplitude of the electrical oscillations but not their frequency (amplitude; 3.7 +/- 0.3 mV, frequency; 0.08 +/- 0.002 Hz). Although a high concentration of ouabain (10(-3) M) (which exhibits non-specific effects) abolished both electrical membrane potential oscillations and vasomotion, we conclude that the Na+-K+ ATPase could not be implicated in the generation of the membrane potential oscillations. We conclude that in rat perfused-pressurized mesenteric artery, the slow wave membrane type of potential oscillation by rhythmically gating voltage-dependent calcium channels, is responsible for the oscillation of intracellular calcium and thus vasomotion.     

Density dependence of respiratory input and transfer impedances in humans

Total respiratory input (Zin) and transfer (Ztr) impedances were obtained from 4 to 30 Hz in 10 healthy subjects breathing air and He-O2. Zin was measured by applying pressure oscillations around the head to minimize the upper airway shunt and Ztr by applying pressure oscillations around the chest. Ztr was analyzed with a six-coefficient model featuring airways resistance (Raw) and inertance (Iaw), alveolar gas compressibility, and tissue resistance, inertance, and compliance. Breathing He-O2 significantly decreased Raw (1.35 +/- 0.32 vs. 1.74 +/- 0.49 cmH2O.l-1.s in air, P less than 0.01) and Iaw (0.59 +/- 0.33 vs. 1.90 +/- 0.44 x 10(-2) cmH2O.l-1.s2), but, as expected, it did not change the tissue coefficients significantly. Airways impedance was also separately computed by combining Zin and Ztr data. This approach demonstrated similar variations in Raw and Iaw with the lighter gas mixture. With both analyses, however, the changes in Iaw were more than what was expected from the change in density. This indicates that factors other than gas inertance are included in Iaw and reveals the short-comings of the six-coefficient model to interpret impedance data.